Page last updated: 2024-10-24

regulation of siRNA processing

Definition

Target type: biologicalprocess

Any process that modulates the frequency, rate or extent of siRNA processing. [GOC:mah]

The regulation of siRNA processing is a complex and tightly controlled process that ensures the accurate and efficient silencing of target genes. This process involves a series of enzymatic steps, including:

1. **Dicer-mediated cleavage:** siRNA duplexes are generated from double-stranded RNA precursors by the RNase III enzyme Dicer. Dicer recognizes and cleaves the dsRNA into short, 21-23 nucleotide siRNAs with 2-nucleotide 3' overhangs.
2. **Loading into RISC:** The siRNA duplex is then loaded into the RNA-induced silencing complex (RISC), a multi-protein complex that mediates gene silencing.
3. **Unwinding of the duplex:** Within RISC, the siRNA duplex unwinds, and the passenger strand is degraded. The guide strand, which is complementary to the target mRNA, remains associated with RISC.
4. **Target mRNA recognition:** The guide strand of the siRNA directs RISC to the target mRNA through base pairing. The binding of the guide strand to the target mRNA is highly specific and depends on perfect or near-perfect complementarity.
5. **Cleavage of the target mRNA:** Once bound to the target mRNA, RISC activates its catalytic activity, typically through Argonaute proteins, which cleave the mRNA within the region targeted by the guide strand.
6. **Degradation of the target mRNA:** The cleaved mRNA is then degraded by cellular exonucleases, preventing its translation into protein.

Several factors regulate siRNA processing and ensure its specificity and efficiency:

* **RNA structure:** The secondary structure of the dsRNA precursor can influence the efficiency of Dicer cleavage. Specific sequences within the dsRNA can also act as recognition signals for Dicer and other processing factors.
* **Small RNA binding proteins:** Various RNA-binding proteins interact with siRNAs and influence their processing and stability. These proteins can promote or inhibit Dicer activity, regulate the loading of siRNAs into RISC, or modulate the stability of the guide strand.
* **Cellular environment:** The cellular environment, including factors like temperature, pH, and the presence of other cellular components, can also impact siRNA processing.
* **Epigenetic modifications:** Epigenetic modifications, such as methylation and acetylation, can affect the accessibility of dsRNA to Dicer and other processing factors.

Regulation of siRNA processing is crucial for maintaining cellular homeostasis and ensuring the proper response to cellular stress and exogenous threats. Misregulation of siRNA processing can lead to dysregulation of gene expression and contribute to various diseases.'
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Proteins (1)

ProteinDefinitionTaxonomy
RISC-loading complex subunit TARBP2A RISC-loading complex subunit TARBP2 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q15633]Homo sapiens (human)

Compounds (2)

CompoundDefinitionClassesRoles
enoxacinenoxacin : A 1,8-naphthyridine derivative that is 1,4-dihydro-1,8-naphthyridine with an ethyl group at the 1 position, a carboxy group at the 3-position, an oxo sustituent at the 4-position, a fluoro substituent at the 5-position and a piperazin-1-yl group at the 7 position. An antibacterial, it is used in the treatment of urinary-tract infections and gonorrhoea.

Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID.
1,8-naphthyridine derivative;
amino acid;
fluoroquinolone antibiotic;
monocarboxylic acid;
N-arylpiperazine;
quinolone antibiotic
antibacterial drug;
DNA synthesis inhibitor
schisanhenol bschisanhenol B: isolated from kernels of Schisandra rubriflora; structure given in first source
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